In animals a convincing body of literature has shown genetic influences on ethanol-related behaviors including measures of initial sensitivity, voluntary ethanol consumption (VEC), acute functional tolerance (AFT) and withdrawal severity (WS) following chronic ethanol exposure. The proposed studies will identify those genes and/or expression products which mediate genetic differences in VEC, AFT, and WS. Selective breeding procedures will be used to obtain ethanol-avoiding congenic strains of ethanol-preferring C57BL mice. Investigators will use these mice and RFLP and PCR methods to determine quantitative trait loci (QTL) for VEC and correlated behavioral effects of ethanol including locomotor activation and inhibition, and conditioned place-preference. Two other studies will obtain, by selective breeding from a genetically heterogeneous (HS) stock, replicate lines of mice which differ in AFT (HAFT1,2 and LAFT1,2) and in WS (HW1,2 and LW1,2). Specific neurochemical hypotheses for GABAergic, dopaminergic, serotonergic, and peptidergic mediation of these alcohol-related behaviors will be investigated. Identification of the genes and subsequent neuronal and neurochemical processes mediating individual differences in VEC, AFT, and WS will lead ultimately to improved methods of identifying individuals at risk for alcoholism and consequently will enhance methods of prevention and treatment of this major societal problem.